Mettl3-Catalyzed m6A Regulates Histone Modifier and Modification Expression in Self-Renewing Somatic Tissue

September 2023 in “ Science Advances ”

Alexandra M. Maldonado López, Eun Kyung Ko, Sijia Huang, Gina Pacella, Nina Kuprasertkul, C. D'souza, Raúl A. Reyes Hueros, Hui Shen, Julian Stoute, Heidi Elashal, Morgan Sinkfield, Amy Anderson, Stephen M. Prouty, Huabing Li, John T. Seykora, Kathy Fange Liu, Brian C. Capell

Mettl3 N6-methyladenosine m6A hair follicle morphogenesis epidermal progenitors histone modifying enzymes chromatin modifiers epithelial development

Studysummary In this study, deleting the gene Mettl3 in mouse epidermal progenitors resulted in impaired epithelial development and self-renewal, highlighting m<sup>6</sup>A's crucial role in regulating chromatin modifiers and maintaining normal epithelial tissue function. Our plain-language summary of this paper — not a Tressless recommendation.

The study explores the role of Mettl3-catalyzed N6-methyladenosine (m6A) in regulating gene expression and chromatin modifiers in self-renewing somatic tissues, focusing on epithelial development. By deleting Mettl3 in mice epidermal progenitors, researchers observed significant developmental issues, such as impaired hair growth and malformed hair follicles, highlighting Mettl3's critical role in epithelial development. The absence of Mettl3 led to transcriptional dysregulation, with nearly 4000 genes showing differential expression, affecting pathways related to keratinization, differentiation, and cell adhesion. The study underscores the importance of Mettl3 and m6A in maintaining epithelial homeostasis and suggests potential therapeutic targets for epithelial diseases and cancers by modulating Mettl3 activity.

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